The long term objective is to elucidate the biochemical properties of cholinesterases in the plaques and tangles of Alzheimer's disease. Anatomical, pathological, histochemical, biochemical, immunohistochemical and ultrastructural methods will be used to identify the unique properties of plaque and tangle-bound cholinesterases. This is and important objective because recent observations have revealed a selective and universal enhancement of cholinesterase activity in all plaques and tangles. Furthermore, it appears that these cholinesterases are different from the cholinesterases may thus play an important role in the pathogenesis of Alzheimer's disease. As part of this research, cholinesterase inhibitors that are optimally suited to inhibit the type of cholinesterases associated with plaques and tangles will be sought and identified. Cholinesterase inhibitors with this type of activity profile may be more effective than currently available substances for the treatment of Alzheimer's disease.